Hydrogen peroxide negatively modulates Wnt signaling through downregulation of β-catenin

Soon Young Shin, Chang Gun Kim, Eek Hoon Jho, Myung Sun Rho, Yong Sik Kim, Young Ho Kim, Young Han Lee

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

The Wnt signal transduction pathway plays an important role in organogenesis and carcinogenesis. In an effort to better understand the action of oxidative stress-induced cellular signaling, we investigate the effect of exogenous H 2O 2 on the Wnt signal pathway. H 2O 2 decreases the amount of nuclear β-catenin and Tcf/Lef-dependent transcription. Overexpression of Dvl-1 abrogated H 2O 2-induced downregulation of β-catenin. Pretreatment with LiCl or Wnt-3a conditioned medium completely inhibited H 2O 2-induced release of mitochondrial cytochrome c and DNA fragmentation. These results suggest that H 2O 2 negatively modulates the Wnt signal pathway through downregulation of β-catenin.

Original languageEnglish
Pages (from-to)225-231
Number of pages7
JournalCancer Letters
Volume212
Issue number2
DOIs
StatePublished - 30 Aug 2004

Keywords

  • Cytochrome c
  • DNA fragmentation
  • Disheveled
  • Hydrogen peroxide
  • Tcf/Lef
  • Wnt-3a
  • β-Catenin

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